Three determinants of renin release: 1. Decreased ❌ sensed by kidney 2. Decreased BP or renal ❌ 3. ❌ receptor activation
Angiotensin causes profound vasoconstriction and aldosterone release.
Both ACEIs and ARBS will decrease systemic vascular resistance and increase renal perfusion.
Diuretics for CKD: 1. Loop diuretics inhibit the activity of the Na-K-2Cl symporter in the ❌. Therefore maximum effect is ~❌%. 2. Thiazide diuretics inhibit the activity of the Na-Cl symporter in the ❌. Maximum effect is ~❌%. 3. K-sparing diuretics inhibit the activity of epithelial Na+ channels in the ❌. Maximum effect is ~❌%. 4. Aldosterone antagonists competitively inhibit the binding of ❌ to the mineralocorticoid receptor. The only class of diuretics that do not enter the tubule cell from the apical (❌) side, and instead from the basolateral (❌) side.
Classification of CKD: • Normal/ CKD 1: GFR >90 mL/min • Mild/ CKD 2: GFR ❌ mL/min • Moderate/ CKD 3: GFR ❌ mL/min • Severe/ CKD 4: GFR ❌ mL/min • End-stage/ CKD 5: GFR <15 mL/min
Non-pharmacological treatment of CKD entails dietary sodium restriction, and protein restriction if GFR < 30mL/min.
When using ACEIs and ARBs in CKD the target is a reduction in urine ❌ of 30-50%. Starting can ❌ GFR; start at a ❌ dose and titrate the dose slowly to effect. Other Important side effects to consider: • ❌kalaemia • ❌ renal impairment • Dry cough (fairly ❌) • Angioedema (❌, but serious)
Methods of estimating renal function: 1. Creatinine-based methods (CLcr, eGFR) • Collection of 24 hour urine samples (❌ clearance) • Cockcroft-Gault ❌ (an estimate of creatinine clearance) • MDRD • CKD-EPI All these are reported by the lab as “❌”. 2. Cystatin C clearance 3. Clearance of a ❌: Inulin (NOT insulin), 51Cr EDTA (radioisotope)
Creatinine is freely filtered by the glomerulus and so its clearance lets us estimate GFR.
Cockcroft & Gault equation: CLcr = ( (140 - ❌) x ❌ x K* ) / ❌
* K = 1.23 for males, 1.04 for females
All creatinine-based methods; • Are poor predictors of GFR if malnourished or low ❌ mass • Over-estimate GFR in the elderly, ❌ (using total body weight), severe or end-stage renal disease • Not for <❌ years old • Unreliable when renal function ❌ rapidly (acute renal failure) • Drugs ❌ tubular secretion can raise creatinine conc (e.g. probenecid, trimethoprim, spironolactone)
In CKD, K+ secretion is ❌ resulting in accumulation. Concentrations above ❌mmol/L become symptomatic. Hyperkalaemia is more likely to be observed in CKD 4 or 5, and is exacerbated by ❌ and K-sparing diuretics.
Match the ranges. - Creatinine (plasma): Adult male: 50-❌ µmol/L, Adult female: 45-❌ µmol/L - Urea (plasma): Adults: ❌ mmol/L - Sodium (plasma) ❌ mmol/L - Osmolality (plasma) 280-❌ mmol/kg - Osmolality (urine) 300-❌ mmol/kg
